In May 2011, hepatitis C virus (HCV) protease inhibitors (PIs) were approved by the US Food and Drug Administration to treat persons with genotype 1 chronic hepatitis C virus (HCV) infection, but not those dually infected with human immunodeficiency virus (HIV). Although critical safety and efficacy data are lacking, the availability of the drugs and substantial medical need justify the off-label use of HCV PIs in select HIV/HCV-coinfected persons. Pending results of ongoing investigations, this article represents provisional guidance on the use of HCV PIs in HIV-infected persons.